Patent GB-881334-A (GB)
Title: Steroid compounds, preparation thereof and compositions thereof
IPC: C12P33/00
Filed: 1959-11-27
Abstract: The invention comprises compounds having the formula <FORM:0881334/IV (b)/1> and the D 1,4 analogues thereof, wherein X is hydrogen, halogen, methoxyl or ethoxyl; B is acarbonyl or b -hydroxymethylene radical; R is hydrogen or an acyl radical of a hydrocarbon carboxylic acid containing 1-8 carbon atoms, inclusive, and the 6-fluoro is a 6a - or 6b -epimer, and processes for the preparation thereof by subjecting a 16-methylated sapogenin e.g. 16-methyl diosgenin to degradation to obtain 16b  - methyl - D 5,16 - pregnadiene - 3 - ol - 20 - one-3-acetate II, reducing II to obtain the corresponding 16b -methyl-D 5-pregnene derivative III which on enol acetylation yields the corresponding 16b -methyl-D 5,17(20)-pregnadiene-3,20-diacetate diacetate IV; treating IV with H2O2 or an organic peracid to obtain the corresponding 5a ,6a -17a ,20a -dioxido derivative V which upon alkaline hydrolysis gives 5a ,6a -oxido-16b -methyl-allopregnane-3b ,17a -diol-20-one VI; converting VI by means of bromine, potassium acetate and potassium iodide into 5a ,6a -oxido-16b -methyl-allo-pregnane-3b , 17a ,21-triol-20-one 21-acetate VII; treating VII with HF to obtain 6b -fluoro-16b -methyl-allo-pregnane-3b ,5a ,17a ,21-tetrol-20-one 21-acetate VIII; oxidising VIII to obtain the 3-keto compound IX, which on dehydration gives the 6b -fluoro-16b -methyl-D 4-pregnene-17a , 21-diol-3,20-dione-21-acetate X; epimerising X to obtain the 6a -fluoro compound XI; hydroxylating to obtain an 11-hydroxy compound XII followed by dehydration to obtain 6 - fluoro - 16b  - methyl - D 4,9(11) - pregnadiene - 17a ,21-diol-3,20-dione-21-acetate XIII; treating XIII with a hypohalogenating agent to obtain the corresponding 9a -halo compound XIV, which with potassium acetate gives 6-fluoro-9b ,11b -oxido-16b -methyl compound; treating the 9b ,11b -oxido compound with hydrogen halide or an alcohol gives the 9a -halo or 9a -alkoxy compounds respectively.  Treatment with selenium dioxide gives the analogous D 1,4-compounds. Oxidation of the 11b -hydroxy compounds gives the corresponding 11-keto compounds. Illustrative products of the invention are 6a -fluoro-16b -methyl - D 4 - pregnene - 17a ,21 - diol - 3,11,20 - trione, 6a ,9a  - difluoro - 16b  - methyl - D 4 - pregnene - 17a ,21 - diol - 3,11,20 - trione, 6a -fluoro - 16b  - methyl - D 4 - pregnene - 11b ,17a ,21 - triol - 3,20 - dione, 6a ,9a  - difluoro - 16b  - methyl - D 4 - pregnene - 11b ,17a ,21 - triol - 3,20 - dione, the 21-acetates thereof and the corresponding D 1,4 compounds.  Specifications 769,998 and 770,000 are referred to.ALSO:A pharmaceutical composition comprises a compound of the formula <FORM:0881334/VI/1> or the D 1,4 analogues thereof, wherein X is hydrogen, halogen, methoxyl or ethoxyl; B is a carbonyl or b -hydroxymethylene radical; R is hydrogen or an acyl radical of a hydrocarbon carboxylic acid containing 1-8 carbon atoms inclusive; and the 6-fluoro atom is the 6a - or 6b -epimer.  Such compositions may be employed orally as pills, tablets, capsules, solutions, syrups and elixirs, in liquid forms for injectable products, or topically as ointments or creams.  Specifications 769,998 and 770,000 are referred to.